guiding treatment changes in Stage IVs by phenotyping their CTCs...for those running

[Lani]

out of options

Perhaps you are no longer responding to antiher therapy because your mets are no longer her2+

If your mets are readily accessible and biopsiable, that may guide any change in treatment as her2+ primaries are associated with her2- mets ( I have previously posted several articles on discordance rates of her2/ER/PR between primary and mets

If not, here is a paper utilizing the FDA approved cell search method looking at CTCs (it misses ctcs which are EPCAM negative) but is the only approved CTC testing.

It suggests a larger multicenter trial and that might be something to look out for

Don't know how this will turn out, as Stephanie Jeffrey @ Stanford utilized a Mag Sweep CTC technology which does not depend on EPCAM for CTC selection and has found tremendous heterogeneity in CTCs in Stage IV her2+ bc patients on anti her2 therapy including, but not only, triple negative CTCs

I still maintain bone marrow sampling has been shown to be better at predicting/phenotyping in what guise (phenotype) Stage IV disease is existing . It ostensibly shows those cells that have shown an ability to survive outside the primary tumor and thrive (and then sleep, awaiting a more opportune time to spread) whereas only a tiny percent of the circulating tumor cells may have that capacity ie they may end up homeless losers and die, whereas their brethren in the bone marrow have shown their ingenuity and ability to survive in difficult environments and therefore represent a much more clear and present danger threat.

BMC Cancer. 2013 Apr 23;13(1):202. [Epub ahead of print]

Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker.

Liu Y, Liu Q, Wang T, Bian L, Zhang S, Hu H, Li S, Hu Z, Wu S, Liu B, Jiang Z.

Abstract
BACKGROUND:
This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients.
METHODS:
Sixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic treatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS) of the patients was estimated using Kaplan-Meier survival curves.

RESULTS:
CTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs (2.5 vs. 7.5 months, P = 0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry (IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients undergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P = 0.002). Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P = 0.001). Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P = 0.499).
CONCLUSIONS:
Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients. To test this idea, additional large cohort, multi-center and prospective clinical trials are needed.
PMID: 23617715